Csk and BatK show opposite temporal expression in the rat CNS: consistent with its late expression in development, BatK induces differentiation of PC12 cells.
BatK is a second member of the Csk family of regulatory kinases that phosphorylate a key inhibitory tyrosine on Src family kinases, leading to down-regulation. To investigate the roles of BatK and Csk, both of which are expressed in the brain, we compared their temporal expression patterns during development of the central nervous system (CNS) in rats. BatK mRNA is undetectable at embryonic day 12 (E12), appears in the developing nervous system at approximately E15, and its expression progressively increases up to the time of birth, thereafter remaining high throughout the adult brain. In striking contrast, Csk is highly expressed throughout embryonic development and remains high in the CNS until birth. It is then dramatically down-regulated in the adult brain except in the olfactory bulb. BatK and Csk thus exhibit complementary temporal expression patterns. Since BatK expression correlates with late-stage development and terminal differentiation, we speculated that it might be involved in regulating neuronal differentiation. Using PC12 cells as a model system, we show that overexpression of BatK is sufficient to induce neurite outgrowth in the absence of nerve growth factor. Further, overexpression of BatK activates the mitogen-activated protein kinase cascade. We propose a model suggesting that, despite overlapping in vitro activities, BatK and Csk regulate different targets in vivo and have different functions during and after neuronal development, BatK being the dominant regulator of Src kinases in the fully differentiated adult brain.
Kuo
S S
SS
Department of Neuroscience, Genentech, Inc., South San Francisco, CA 94080, USA.
Armanini
M P
MP
Phillips
H S
HS
Caras
I W
IW
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D015139:Blotting, Southern; D001973:Bromodeoxyuridine / Q000494:pharmacology; D000081247:CSK Tyrosine-Protein Kinase; D002454:Cell Differentiation / Q000187:drug effects; D002490:Central Nervous System / Q000254:growth & development* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005822:Genetic Vectors; D017403:In Situ Hybridization; D009414:Nerve Growth Factors / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D014162:Transfection; D018909:src Homology Domains; D019061:src-Family Kinases
D000963:Antimetabolites; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C091243:Matk protein, rat; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D001973:Bromodeoxyuridine